Donepezil loaded PLGA-b-PEG nanoparticles: their ability to induce destabilization of amyloid fibrils and to cross blood brain barrier in vitro

Abstract

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Cholinesterase inhibitors (ChEIs) are commonly used for symptomatic treatment of neural transmission improvement in AD. Donepezil is a reversible and non-competitive ChEI which is clinically used for palliative treatment of AD. The aim of the present study was to investigate the destabilizing effect of donepezil loaded poly(lactic-co-glycolic acid)-block-poly (ethylene glycol) [PLGA-b-PEG] nanoparticles on fibril formation in vitro and the ability of these nanoparticles to cross blood brain barrier (BBB) using in vitro BBB model and the neuroprotective effects of free donepezil and donepezil loaded PLGA-b-PEG nanoparticles. Donepezil loaded PLGA-b-PEG nanoparticles were prepared with double emulsion method. Destabilizing effect of these donepezil loaded particles on the amyloid-beta fibril (Aβ and Aβ) formation was determined in vitro. Nanoparticles were found to have small particle size and have destabilizing effect on fibril formation. In vitro BBB model was successfully prepared. Nanoparticles showed the ability to cross the BBB and showed a controlled release profile in this system. IL-1β, IL-6, GM-CSF, TGF-β, MCP-1 and TNF-α levels were found to be increased in both gene and protein expression levels in astrocytes incubated with amyloid fibrils in in vitro BBB model suggesting an increased inflammation. Free donepezil and donepezil loaded nanoparticle administration caused a significant dose-dependent decrease in both gene and protein expression levels of IL-1β, IL-6, GM-CSF and TNF-α. No significant changes were observed for TGF-β and MCP-1.

Honeycomb-like PLGA-b-PEG Structure Creation with T-Junction Microdroplets

“…This discrepancy can be explained by the solubility difference between two solvents. Although both chloroform and DCM are known to be immiscible in water phase, the solubility of DCM is more than two times bigger than chloroform at ambient temperature, which makes DCM much more favoured in conventional nanoparticle synthesis [36][37] . The Marangoni number (Ma) equation, which is defined as the proportion of thermal/surface tension forces divided by viscous forces is:…”

Nano Carrier Drug Delivery Systems for the Treatment of Neuropsychiatric Disorders: Advantages and Limitations

“…The development of chitosan nanosuspension for intranasal administration [178] and the chitosan intranasal form of donepezil [235] promoted the usage of lower drug dose. Along with these nanoparticles LGA-b-PEG by Baysal et al and liposomes by Al Asmari et al were constructed for this drug [177,180].…”

Design, Synthesis and Biological Assessment of Novel 2‐(4‐Alkoxybenzylidine)‐2,3‐dihydro‐5,6‐dimethoxy‐1H‐inden‐1‐one Derivatives as hAChE and hBuChE Enzyme Inhibitors

“…Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a selective loss of cholinergic neurons of the central nervous system (CNS) and decreasing levels of acetylcholine (ACh) . At the moment, AD affects over 20 million people all around the world and increases with growth in the aging population; as expected to be double in 20 years .…”

“…Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a selective loss of cholinergic neurons of the central nervous system (CNS) and decreasing levels of acetylcholine (ACh). [1][2][3][4] At the moment, AD affects over 20 million people all around the world and increases with growth in the aging population; as expected to be double in 20 years. [5,6] The exact cause of the disease has not been identified yet; it is considered a multifactorial disease with a combination of genetic, aging and environmental factors.…”